SearcharxivSearch

arXiv subjects

Yann Perrot

Publications and source records attributed to Yann Perrot.

4 recordsLinked to original sources

Integrating nano- and micrometer-scale energy deposition models for mechanistic prediction of radiation-induced DNA damage and cell survival

We present an integrated modeling framework that combines the Generalized Stochastic Microdosimetric Model (GSM2), used to predict cell survival fractions, with MINAS-TIRITH, a fast and efficient Geant4 DNA-based tool for simulating radiation-induced DNA damage in cell populations. This approach enables the generation of spatially and structurally resolved double-strand break (DSB) distributions, capturing key features such as damage complexity and chromosome specificity. A novel application of the DBSCAN clustering algorithm is introduced to group DSBs at the micrometer scale. This allows the identification of physical aggregates of DNA damage and their association with subnuclear domains, providing a direct link to the cell survival probability as predicted by \gsm. The model was validated using experimental data from HUVEC cells irradiated with 220 kV X-rays and H460 cells exposed to protons over a wide linear energy transfer (LET) range, from approximately 4 keV/{\mu}m to over 20 keV/{\mu}m. Results show excellent agreement between simulations and experimental survival probabilities, making this one of the first consistent multi-scale models to bridge nanodosimetric and microdosimetric representations of radiation with biological outcomes such as cell survival. By incorporating the inherent stochastic nature of radiation-matter interactions, this framework effectively connects the physical properties of the radiation field to the biological response at the cellular level. Its accuracy across various radiation types and energies supports its potential for use in biologically optimized radiotherapy.

physics.bio-ph

Evaluation of the uncertainty in calculating nanodosimetric quantities due to the use of different interaction cross sections in Monte Carlo track structure codes

This study evaluates the uncertainty in nanodosimetric calculations caused by variations in interaction cross sections within Monte Carlo Track Structure (MCTS) simulation codes. Nanodosimetry relies on accurately simulating particle interactions at the molecular scale. Different MCTS codes employ distinct physical models and datasets for electron interactions in liquid water, a surrogate for biological tissues. The paper focuses on the Ionization Cluster Size Distribution (ICSD) generated by electrons of varying energies in nanometric volumes. Seven MCTS codes were tested using their native cross sections and a common dataset derived from averaging data used in the participating codes. The results reveal significant discrepancies among the codes in ICSDs and derived biologically relevant nanodosimetric quantities such as mean ionization numbers (M1) and probabilities of obtaining two or more ionizations (F2). The largest variations were observed for low-energy electrons, where the contribution from interaction cross sections dominates the overall uncertainties. For instance, M1 values for ICSDs of electron of 20 eV can differ by around 45 % (RSD) and 34 % (RSD) was found for F2 values of ICSDs of electrons of 50 eV. Using common cross sections substantially reduced the discrepancies, suggesting that cross section datasets are the primary source of variability. Finally, estimates of deoxyribonucleic acid (DNA) damage using the PARTRAC code highlight tht cross section variations have a non-negligible impact simulated biological outcomes, particularly for double-strand breaks (DSBs) Indeed, despite the fact that many other parameters in the simulation that can greatly differ from one code to another, the different interaction cross-sections studied in this work can lead to differences in the number of DSBs calculated with the PARTRAC code of up to 15%.

physics.med-ph

The Associated Volume sampling algorithm as an alternative method for the calculation of ionisation cluster size distributions in computational nanodosimetry

In computational nanodosimetry, Monte Carlo Track Structure (MCTS) simulations are employed to calculate ionisation cluster size distributions (ICSDs), which are crucial for characterising mixed radiation fields at the nanoscale. The Uniform Sampling (US) algorithm, commonly used for this purpose, is inefficient when evaluating ICSDs conditioned on clusters exceeding a given size $\nu$ threshold. This study investigates a more efficient alternative - the Associated Volume (AV) algorithm - against the US approach for computing conditional ICSDs ($\nu \ge 1$) from proton tracks simulated with Geant4-DNA. Two configurations of the AV algorithm were evaluated: the standard AV-Overlap, allowing sensitive volumes to overlap (with a 1/$\nu$ correction), and the novel AV-No Overlap, which prevents overlap. We compared the conditional ICSDs, mean cluster size ($M_1$), complementary cumulative frequencies ($F_k$ for $k \in [2,7]$), and overall execution time per run and per event. Deviations exceeding two standard deviations of the mean difference were considered statistically significant. Although statistically significant differences in ICSDs, $M_1$ and $F_k$ were observed, the relative differences in the AV-Overlap rarely exceeded 5%, whereas the No Overlap configuration they ranged from $\lt$ 1% to approximately 15% at the higher $F_k$. Both AV configurations achieved execution times one to two orders of magnitude shorter than the US algorithm. Our findings indicate that the AV-Overlap algorithm may be a preferred alternative for calculating conditional ICSDs and derived nanodosimetric quantities, offering a substantial gain in computational efficiency without compromising accuracy.

physics.comp-ph

Intercomparison of micro- and nanodosimetry Monte Carlo simulations: an approach to assess the influence of different cross-sections for low-energy electrons on the dispersion of results

An intercomparison of microdosimetric and nanodosimetric quantities simulated Monte Carlo codes is in progress with the goal of assessing the uncertainty contribution to simulated results due to the uncertainties of the electron interaction cross-sections used in the codes. In the first stage of the intercomparison, significant discrepancies were found for nanodosimetric quantities as well as for microdosimetric simulations of a radiation source placed at the surface of a spherical water scoring volume. This paper reports insight gained from further analysis, including additional results for the microdosimetry case where the observed discrepancies in the simulated distributions could be traced back to the difference between track-structure and condensed-history approaches. Furthermore, detailed investigations into the sensitivity of nanodosimetric distributions to alterations in inelastic electron scattering cross-sections are presented which were conducted in the lead up to the definition of an approach to be used in the second stage of the intercomparison to come. The suitability of simulation results for assessing the sought uncertainty contributions from cross-sections is discussed and a proposed framework is described.

physics.med-ph